Trade-offs between root-secreted acid phosphatase and root morphology traits, and their contribution to phosphorus acquisition in Brassica napus.

Oilseed rape (Brassica napus) is one of the most important oil crops in the world and shows sensitivity to low phosphorus (P) availability. In many soils, organic P (Po) is the main component of the soil P pool. Po must be mineralised to Pi through phosphatases, and then taken up by plants. However, the relationship between root-secreted acid phosphatases (APase) and root morphology traits, two important P-acquisition strategies in response to P deficiency, is unclear among B. napus genotypes. This study aimed to understand their relationship and how they affect P acquisition, which is crucial for the sustainable utilisation of agricultural P resources. This study showed significant genotypic variations in root-secreted APase activity per unit root fresh weight (SAP) and total root-secreted APase activity per plant (total SAP) among 350 B. napus genotypes. Seed yield was positively correlated with total SAP but not significantly correlated with SAP. Six root traits of 18 B. napus genotypes with contrasting root biomass were compared under normal Pi, low Pi and Po. Genotypes with longer total root length (TRL) reduced SAP, but those with shorter TRL increased SAP under P deficiency. Additionally, TRL was important in P-acquisition under three P treatments, and total SAP was also important in P-acquisition under Po treatment. In conclusion, trade-offs existed between the two P-acquisition strategies among B. napus genotypes under P-deficient conditions. Total SAP was an important root trait under Po conditions. These results might help to breed B. napus with greater P-acquisition ability under low P availability conditions.

Genomic and co-expression network analyses reveal candidate genes for oil accumulation based on an introgression population in Upland cotton (Gossypium hirsutum).

KEY MESSAGE: Integrated QTL mapping and WGCNA condense the potential gene regulatory network involved in oil accumulation. A glycosyl hydrolases gene (GhHSD1) for oil biosynthesis was confirmed in Arabidopsis, which will provide useful knowledge to understand the functional mechanism of oil biosynthesis in cotton. Cotton is an economical source of edible oil for the food industry. The genetic mechanism that regulates oil biosynthesis in cottonseeds is essential for the genetic enhancement of oil content (OC). To explore the functional genomics of OC, this study utilized an interspecific backcross inbred line population to dissect the quantitative trait locus (QTL) interlinked with OC. In total, nine OC QTLs were identified, four of which were novel, and each QTL explained 3.62-34.73% of the phenotypic variation of OC. The comprehensive transcript profiling of developing cottonseeds revealed 3,646 core genes differentially expressed in both inbred parents. Functional enrichment analysis determined 43 genes were annotated with oil biosynthesis processes. Implementation of weighted gene co-expression network analysis showed that 803 differential genes had a significant correlation with the OC phenotype. Further integrated analysis identified seven important genes located in OC QTLs. Of which, the GhHSD1 gene located in stable QTL qOC-Dt3-1 exhibited the highest functional linkages with the other network genes. Phylogenetic analysis showed significant evolutionary differences in the HSD1 sequences between oilseed- and starch- crops. Furthermore, the overexpression of GhHSD1 in Arabidopsis yielded almost 6.78% higher seed oil. This study not only uncovers important genetic loci for oil accumulation in cottonseed, but also provides a set of new candidate genes that potentially influence the oil biosynthesis pathway in cottonseed.

Optimal phosphorus management strategies to enhance crop productivity and soil phosphorus fertility in rapeseed-rice rotation.

Optimal phosphorus (P) managements can improve the crop yield without reducing soil P supply capacity over the long term. In this study, the rapeseed-rice rotation experiments were conducted to evaluate the effect of five optimal P fertilizer managements, including the addition of RA (rooting agents), PSB (phosphate solubilizing bacteria), CMP (calcium and magnesium phosphate fertilizer), DP1 (starter P) and DP2 (foliar fertilizer) with the reduction of 40% (in the 1st rapeseed season) and 75% (in the 2nd rapeseed season) P fertilizers of farmers' fertilizer practice (FFP) on crop productivity and soil P fertility in low and high P fertility soils. Seed yield, P partial factor productivity, and P recovery efficiency of both cultivars, Shengguang168 (SG168) and Zhongshuang 11 (ZS11), were significantly improved under optimal P managements, and the increase of them in low P fertility soil was more than that in high P fertility soil. Total P surplus was lower under optimal P managements than under FFP in both P fertility soils. The increasing amount of crop yields under optimal P managements for both cultivars was equivalent to that of 16.0-38.3 kg P2O5 hm-2 of P fertilizer application, and the order of the optimal P managements was as follows: RA > PSB > CMP > DP1 > DP2. In addition, the grain yield of rotated rice cultivar Longliangyou1212 (LLY1212) without P supply was not reduced in both fertility soils. Compared with low P fertility soil, yields of SG168, ZS11 and LLY1212 in high P fertility soil increased by 28.1%-71.7%, 28.3%-78.9% and 26.2%-47.2% at the same treatment, respectively. In summary, optimal P managements in the rapeseed season could stabilize the crop yield, promote P use efficiency and the capacity of soil P supply in the rapeseed-rice rotation, especially in low P fertility soil.

Composition Analysis and Nutritional Value Evaluation of Amino Acids in the Fruit of 161 Jujube Cultivars.

Amino acids are an essential group of compounds involved in protein synthesis and various metabolic and immune reactions in the human body. Chinese jujubes (Ziziphus jujuba Mill.) are an important fruit and medicinal plant which are native to China and have been introduced into around 50 countries. However, systematic research on the composition and content diversity of amino acids in the jujube is still lacking. In this experiment, the amino acid composition and the contents of the dominant amino acids in the fruit of 161 cultivars of jujube were determined by HPLC. Of the twenty-one kinds of amino acids detected, a total of fourteen kinds of amino acids were detected, of which eight kinds of amino acids were relatively high, including five essential amino acids (threonine, valine, isoleucine, leucine, and phenylalanine) and three nonessential amino acids (glycine, alanine, and proline). However, the contents of the remaining six amino acids were relatively low (aspartic acid, glutamic acid, histidine, serine, arginine, and tryptophan). Therefore, the eight primary amino acids were used as the index to evaluate the amino acids of 161 jujube varieties. Proline accounts for 56.8% of the total amino acid content among the eight amino acids. The total content of the eight primary amino acids in most jujube varieties was 1-1.5 g/100 g, and the highest content of 'Zaoqiangmalianzao' was 2.356 g/100 g. The average content of proline was 6.01-14.84 times that of the other seven amino acids. According to the WHO/FAO revised model spectrum of ideal essential amino acids for humans, 19 cultivars met the E/T (essential amino acids/total amino acids) standard, and their values ranged from 35% to 45%; 12 cultivars meet E/NE (non-essential amino acids) ≥ 60%. All cultivars reached the requirement of BC (branched-chain amino acids)/E ≥ 40% with 15 cultivars over 68%. One hundred and fifty-seven cultivars reach the standard of BC/A (aromatic amino acids) ≈ 3.0~3.5. The amino acid ratio coefficient analysis showed that phenylalanine was the first limiting amino acid of all the jujube cultivars. The SRC (the score of amino acid ratio coefficient) values of 134 cultivars were between 50% and 70%, with 12 cultivars over 70%, indicating that jujube fruits are of high nutritional value in terms of amino acids. Based on the principal component analysis and comprehensive ranking of amino acid nutritional value, the top five cultivars were screened from the 161 ones tested, i.e., 'Tengzhouchanghongzao', 'Xinzhengxiaoyuanzao', 'Hanguowudeng', 'Xuputiansuanzao', and 'Lichengxiaozao'. This study established, firstly, a complete basic data analysis of amino acid content in jujube fruit which could be used to select germplasm resources suitable for developing functional amino acid food, and provide theoretical support for the high value utilization of amino acids in jujubes.

Taraxasterol alleviates fatty acid-induced lipid deposition in calf hepatocytes by decreasing ROS production and endoplasmic reticulum stress.

Increased concentrations of free fatty acids (FFAs) induce reactive oxygen species (ROSs) generation and endoplasmic reticulum (ER) stress, thus, increasing the risk of fatty liver in dairy cows during the periparturient period. In non-ruminants, Taraxasterol (Tara; a pentacyclic triterpenoid found in medicinal plants) plays an important role in anti-inflammatory and antioxidant reactions. Whether Tara can alleviate or prevent fatty liver in ruminants is unknown. We addressed whether Tara supply could dampen lipid accumulation, ROSs production, and ER stress caused by FFAs in calf hepatocytes. Primary calf hepatocytes were isolated from five healthy calves (1 d old, female, 30-40 kg, fasting, rectal temperature 38.7-39.7 °C). In the first experiment, hepatocytes were incubated with various concentrations of Tara (2.5, 5, and 10 µg/mL) for 12 h prior to the 1.2-mM FFAs challenge. Results indicated that the level of ROSs was lowest with 5 µg/mL Tara. Thus, to further characterize the molecular mechanisms whereby Tara protects from FFAs-induced lipid deposition in calf hepatocytes, we performed incubations with 5 µg/mL Tara for 12 h prior to a 1.2-mM FFAs challenge for an additional 12 h. Results indicated that 1.2-mM FFAs challenge increased mitochondrial membrane potential (MMP), enhanced expression of proteins and mRNA associated with ER stress (PERK, IRE1, GRP78, ATF6, and CHOP) and fatty acid synthesis (FASN, ACC1, and SREBP-1c), and ultimately led to increased lipid droplet synthesis. In contrast, Tara treatment alleviated these negative effects after 1.2-mM FFAs challenge. To determine whether Tara protects against FFAs-induced lipid droplet synthesis by alleviating oxidative stress, hepatocytes were treated with 5 µg/mL Tara for 22 h prior to H2O2 (440 µM) challenge for 2 h. Compared with H2O2 treatment alone, results revealed a marked decrease in ROSs, MMP, and protein abundance of ER stress (GRP78, ATF6, and CHOP) and lipid droplet synthesis in response to Tara prior to H2O2 challenge. Data suggested that the increase in mitochondrial ROSs production contributes to lipid accumulation in calf hepatocytes. Collectively, our in vitro data indicate that Tara alleviates fatty acid-induced lipid deposition. Further research is warranted to ascertain that Tara can be helpful in the therapeutic management of early lactating cows to control or alleviate excessive hepatic lipid deposition.

Fatty liver is a common occurrence in the early postpartum period, partly due to the large influx of fatty acids into the liver during adipose tissue lipolysis. Because there is a linkage between fatty acid metabolism, oxidative stress, and lipid deposition in hepatocytes of nonruminant animals, we evaluated the potential therapeutic roles of Taraxasterol on reactive oxygen species and endoplasmic reticulum (ER) stress in vitro. This compound found in medicinal plants alleviated oxidative and ER stress and reduced lipid accumulation. Thus, it may represent a novel therapeutic tool for the management of dairy cows around parturition.

[Optimization of extraction process of Congrong Shujing Granules based on AHP-CRITIC analysis].

The index weight coefficients were determined by comparing the analytic hierarchy process(AHP), the criteria importance through inter-criteria correlation(CRITIC), and the AHP-CRITIC mixed weighting method. The comprehensive scores of index components(echinacoside, salvianolic acid B, paeoniflorin, and ointment yield) of each group in the orthogonal test were compared to optimize the extraction process of Congrong Shujing Granules. The results showed that the AHP-CRITIC mixed weighting method scientifically optimized the extraction process. To be specific, the decoction pieces should be added with the 6-fold amount of water and extracted twice, 1 h each time. After three verification tests, the average mass fractions of echinacoside, salvianolic acid B, and paeoniflorin were 0.72, 9.34, and 5.92 mg·g~(-1), respectively, and the average ointment yield was 47.18%. As verified by the AHP-CRITIC mixed weighting method and the orthogonal test, the optimized extraction process of Congrong Shujing Granules was stable and feasible and could be applied to industrial production.

Identification and Characterization of WRKY41, a Gene Conferring Resistance to Powdery Mildew in Wild Tomato (Solanum habrochaites) LA1777.

WRKYs, a large family of transcription factors, are involved in plant response to biotic and abiotic stresses, but the role of them in tomato resistance to Oidium neolycopersici is still unclear. In this study, we evaluate the role of WRKYs in powdery mildew-resistant wild tomato (Solanum habrochaites) LA1777 defense against O. neolycopersici strain lz (On-lz) using a combination of omics, classical plant pathology- and cell biology-based approaches. A total of 27 WRKYs, belonging to group I, II, and III, were identified as differentially expressed genes in LA1777 against On-lz. It was found that expression of ShWRKY41 was increased after Pseudomonas syringae pv. tomato (Pst) DC3000, On-lz and Botrytiscinerea B05 inoculation or ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) treatment. GUS staining of ShWRKY41 promoter indicated that the expression of ShWRKY41 could be induced by SA and ethylene. Furthermore, ShWRKY41 gene silencing reduced the resistance to On-lz infection by decreasing the generation of H2O2 and HR in LA1777 seedlings. Overall, our research suggests that ShWRKY41 plays a positive role in defense activation and host resistance to O. neolycopersici in wild tomato (S. habrochaites) LA1777.

QiangGuYin Modulates the OPG/RANKL/RANK Pathway by Increasing Secretin Levels during Treatment of Primary Type I Osteoporosis.

QiangGuYin (QGY) is a common Traditional Chinese medicine prescription for the treatment of osteoporosis. Previous clinical studies have found that QGY effectively improves bone mineral density (BMD) in postmenopausal women, but its underlying mechanism remains unclear. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK) pathway is a classic pathway involved in osteoporosis. Secretin levels are a serum marker of osteoporosis, but their effect on the OPG/RANKL/RANK pathway has not been reported. Hence, we investigated the relationship between the OPG/RANKL/RANK pathway and secretin and further revealed the mechanism underlying the effect of QGY in the treatment of osteoporosis. Mice were divided into secretin knockdown, secretin overexpression, and corresponding control groups. Micro-computed tomography was used to detect BMD in different groups, and the results show that QGY significantly improved BMD in mice of the secretin knockdown group. To further verify this, the serum levels of OPG, RANKL, RANK, and secretin were measured by enzyme-linked immunosorbent assays, and femur levels of OPG, RANKL, RANK, and secretin were evaluated by real-time quantitative PCR and western blotting. The results show that the expression of OPG was inhibited and that of RANKL and RANK was increased in mice from the secretin knockdown group, whereas the expression of OPG was upregulated and that of RANKL and RANK was downregulated after QGY intervention. Therefore, QGY inhibited bone resorption by promoting the expression of secretin and modulating the OPG/RANKL/RANK pathway. In addition to the effect of QGY, we also revealed the general regulatory effect of secretin on the OPG/RANKL/RANK pathway. We conclude that QGY modulates the OPG/RANKL/RANK pathway by increasing secretin levels during treatment of primary type I osteoporosis. This work provides a theoretical basis for the clinical use of QGY in the treatment of osteoporosis.

Genome-wide association study dissects the genetic control of plant height and branch number in response to low-phosphorus stress in Brassica napus.

BACKGROUND AND AIMS: Oilseed rape (Brassica napus) is one of the most important oil crops worldwide. Phosphorus (P) deficiency severely decreases the plant height and branch number of B. napus. However, the genetic bases controlling plant height and branch number in B. napus under P deficiency remain largely unknown. This study aims to mine candidate genes for plant height and branch number by genome-wide association study (GWAS) and determine low-P-tolerance haplotypes. METHODS: An association panel of B. napus was grown in the field with a low P supply (P, 0 kg ha-1) and a sufficient P supply (P, 40 kg ha-1) across 2 years and plant height and branch number were investigated. More than five million single-nucleotide polymorphisms (SNPs) were used to conduct GWAS of plant height and branch number at two contrasting P supplies. KEY RESULTS: A total of 2127 SNPs were strongly associated (P < 6·25 × 10-07) with plant height and branch number at two P supplies. There was significant correlation between phenotypic variation and the number of favourable alleles of associated loci on chromosomes A10 (chrA10_821671) and C08 (chrC08_27999846), which will contribute to breeding improvement by aggregating these SNPs. BnaA10g09290D and BnaC08g26640D were identified to be associated with chrA10_821671 and chrC08_27999846, respectively. Candidate gene association analysis and haplotype analysis showed that the inbred lines carrying ATT at BnaA10g09290Hap1 and AAT at BnaC08g26640Hap1 had greater plant height than lines carrying other haplotype alleles at low P supply. CONCLUSION: Our results demonstrate the power of GWAS in identifying genes of interest in B. napus and provided insights into the genetic basis of plant height and branch number at low P supply in B. napus. Candidate genes and favourable haplotypes may facilitate marker-based breeding efforts aimed at improving P use efficiency in B. napus.

[Preparation of paclitaxel-loaded and folic acid-modified poly (lactic-co-glycolic acid) nano-micelles and in vitro anticancer effect on cervical cancer HeLa cells].

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 µg·mL~(-1) and 0.66 µg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.

Yi-Qi-Jian-Pi-Xiao-Yu-Xie-Zhuo Formula Improves Muscle Atrophy via Modulating the IGF-1/PI3K/Akt Signaling Pathway in 5/6 Nephrectomized Rats.

The Yi-Qi-Jian-Pi-Xiao-Yu-Xie-Zhuo (YQJPXYXZ) formula has been used for treating chronic kidney disease (CKD) for many years with good efficiency based on the cumulative empirical experience of previous practitioners. Impairment of the IGF-1/PI3K/Akt signaling pathway plays an important role in mediating muscle wasting. This study aimed to observe effects of the YQJPXYXZ formula on muscle atrophy in CKD rats and investigate its possible mechanism on regulation of the IGF-1/PI3K/Akt signaling pathway. The 5/6 nephrectomized rats were randomly allocated into 3 groups: the CKD group, the KT (compound α-ketoacid tablets) group, and the YQJPXYXZ group. Besides, sham-operated rats were included as the sham group. All rats were treated for 12 weeks. Results showed that administration of the YQJPXYXZ formula prevented body weight loss and muscle fiber size decrease. Moreover, the YQJPXYXZ formula increased the IGF-1 level of serum and skeletal muscle in CKD rats and enhanced the phosphorylation level of Akt. Furthermore, the YQJPXYXZ formula decreased the Atrogin1 and MuRF1 mRNA and MuRF1 proteins. In conclusion, our data demonstrated that the YQJPXYXZ formula improves muscle wasting in CKD rats, which might be associated with the modulation of the IGF-1/PI3K/Akt signaling pathway and inhibition of the ubiquitin-proteasome system (UPS).

Integrated Methylome and Transcriptome Analysis between the CMS-D2 Line ZBA and Its Maintainer Line ZB in Upland Cotton.

DNA methylation is an important epigenetic modification involved in multiple biological processes. Altered methylation patterns have been reported to be associated with male sterility in some plants, but their role in cotton cytoplasmic male sterility (CMS) remains unclear. Here, integrated methylome and transcriptome analyses were conducted between the CMS-D2 line ZBA and its near-isogenic maintainer line ZB in upland cotton. More methylated cytosine sites (mCs) and higher methylation levels (MLs) were found among the three sequence contexts in ZB compared to ZBA. A total of 4568 differentially methylated regions (DMRs) and 2096 differentially methylated genes (DMGs) were identified. Among the differentially expressed genes (DEGs) associated with DMRs (DMEGs), 396 genes were upregulated and 281 genes were downregulated. A bioinformatics analysis of these DMEGs showed that hyper-DEGs were significantly enriched in the "oxidative phosphorylation" pathway. Further qRT-PCR validation indicated that these hypermethylated genes (encoding the subunits of mitochondrial electron transport chain (ETC) complexes I and V) were all significantly upregulated in ZB. Our biochemical data revealed a higher extent of H2O2 production but a lower level of adenosine triphosphate (ATP) synthesis in CMS-D2 line ZBA. On the basis of the above results, we propose that disrupted DNA methylation in ZBA may disrupt the homeostasis of reactive oxygen species (ROS) production and ATP synthesis in mitochondria, triggering a burst of ROS that is transferred to the nucleus to initiate programmed cell death (PCD) prematurely, ultimately leading to microspore abortion. This study illustrates the important role of DNA methylation in cotton CMS.

Effects of ORAI calcium release-activated calcium modulator 1 (ORAI1) on neutrophil activity in dairy cows with subclinical hypocalcemia1.

Hypocalcemia in dairy cows is often associated with inflammation-related disorders such as metritis and mastitis. The protein encoded by the Ca2+ release-activated calcium modulator 1 (ORAI1) gene is a membrane Ca2+ channel subunit that is activated when Ca2+ stores are depleted. Polymorphonuclear neutrophils (PMNL) have a crucial role in the defense against infection through migration, adhesion, chemotaxis, phagocytosis, and reactive oxygen species (ROS) production in response to pathogens. Whether hypocalcemia affects the activity of PMNL and if ORAI1 is involved remains unknown. To address this, PMNL were isolated at 3 d of calving from dairy cows diagnosed as clinically healthy (n = 20, CONTROL) or with plasma concentration of calcium < 2.0 mmol/L as a criterion for diagnosis of subclinical hypocalcemia (n = 20, HYPOCAL). PMNL isolated from both groups of cows were treated with or without the sarcoendoplasmic Ca2+ ATPase inhibitor thapsigargin, Ca2+ ionophore Ionomycin, and ORAI1 blocker 2APB. The intracellular Ca2+ concentration, ORAI1 abundance, ROS, phagocytosis rate, migration, and adhering capacity of treated PMNL were evaluated. Some of the in vitro assays also included use of small interfering ORAI1 RNA (siORAI1), 100 nM 1,25(OH)2D3, or 100 nM parathyroid hormone (PTH). Intracellular Ca2+ concentration was markedly lower in HYPOCAL. In addition, ORAI1 was detected in PMNL plasma membrane via FACS and was markedly lower in cows with HYPOCAL. Migration, adhesion capacity, and phagocytosis rate of PMNL were lower in response to HYPOCAL. Furthermore, plasma and PMNL concentration of nucleosome assembly protein (NAP2) and pro-platelet basic protein (CXCL7) was markedly lower with HYPOCAL. All these changes were associated with lower ROS production by PMNL. Thapsigargin and ionomycin treatment in vitro increased ORAI1 expression, migration of PMNL, adhering capacity, phagocytosis rate, and ROS production; conversely, those effects were abrogated by siORAI1 and ORAI1 inhibitor 2APB treatment. Also cytosolic Ca2+ concentration and ORAI1 abundance were increased by 1,25(OH)2D3 and PTH supplementation. Overall, the data indicate that failure of PMNL to uptake Ca2+ due to downregulation of ORAI1 during subclinical hypocalcemia is a factor contributing to impaired PMNL function. In addition, plasma PTH or 1,25(OH)2D3 could regulate ORAI1 and also participate in the regulation of PMNL activity.

Bao Yuan decoction and Tao Hong Si Wu decoction improve lung structural remodeling in a rat model of myocardial infarction: Possible involvement of suppression of inflammation and fibrosis and regulation of the TGF-ß1/Smad3 and NF-κB pathways.

Chronic heart failure (CHF) leads to pulmonary structural remodeling, which may be a key factor for poor clinical outcomes in patients with end-stage heart failure, and few effective therapeutic options are presently available. The aim of the current study was to explore the mechanism of action and pulmonary-protective effects of treatment with Bao Yuan decoction combined with Tao Hong Si Wu decoction (BYTH) on lung structural remodeling in rats with ischemic heart failure. In a model of myocardial infarction (MI) induced by ligation of the left anterior descending (LAD) artery, rats were treated with BYTH. Heart function and morphometry were measured followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. The levels of transforming growth factor-ß1 (TGF-ß1), type I collagen, phosphorylated-Smad3 (p-Smad3), tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), active nuclear factor κB (NF-κB) and alpha smooth muscle actin (α-SMA) were detected using Western blotting. Lung weight increased after an infarct with no evidence of pulmonary edema and returned to normal as a result of BYTH. In addition, BYTH treatment reduced levels of type I collagen, TGF-ß1, and α-SMA expression and decreased the phosphorylation of Smad3 in the lungs of rats after MI. BYTH treatment also reduced the elevated levels of lung inflammatory mediators such as TNF-α, TLR4, and NF-κB. Results suggested that BYTH could effectively improve lung structural remodeling after MI because of its anti-inflammatory and anti-fibrotic action, which may be mediated by suppression of the TGF-ß1/Smad3 and NF-κB signaling pathways.

Is the Wedged Insole an Effective Treatment Option When Compared with a Flat (Placebo) Insole: A Systematic Review and Meta-Analysis.

BACKGROUND: Using the lateral wedge insole is a conservative management strategy for knee osteoarthritis. The theoretical basis for this intervention is to correct femorotibial angle, thereby reducing pain and optimising function. OBJECTIVE: This systematic review evaluates the evidence on the effectiveness of wedge insole compared with flat insole for the treatment of knee osteoarthritis. METHODS: A systematic review was performed, searching published (MEDLINE, EMBASE, CNKI, Cochrane Library, and Web of Science) and unpublished literature from their inception to April 2018. Randomized controlled trials (RCTs) that compared the use of wedge insole with a flat insole were included. Risk of bias and clinical relevance were assessed, and outcomes were analysed through meta-analysis. RESULT: From a total of 413 citations, 8 studies adhered to the a priori eligibility criteria. The WOMAC pain was shown to be statistically nonsignificant change with the use of wedge insole (SMD=0.07), and low heterogeneity (I2=22%) and a 95% CI that crossed zero (95% CI: -0.09 to 0.24). The 5 independent trials were not significant in improving pain score (SMD = -0.02, 95% CI: -0.19 to 0.16). This review also revealed no significance in improving Lequesne index (SMD = -0.27, 95% CI: -0.72 to 0.19). The meta-analysis from the 2 independent trials was significant in improving femorotibial angle (SMD = -0.41, 95% CI: -0.73 to -0.09). In conclusion, this meta-analysis suggested that lateral wedge insoles can improve femorotibial angle but are of no benefit with pain and functions in knee osteoarthritis.

Arctigenin Attenuates Learning and Memory Deficits through PI3k/Akt/GSK-3ß Pathway Reducing Tau Hyperphosphorylation in Aß-Induced AD Mice.

Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Our previous study demonstrated that arctigenin exerts neuroprotective effects both in vitro and in vivo in a Parkinson's disease model. However, the exact mechanism through which arctigenin improves amyloid beta-induced memory impairment by inhibiting the production of the hyperphosphorylated tau protein is unknown. Amyloid ß1-42 was slowly administered via the intracerebroventricular route in a volume of 3 µL (≈ 410 pmmol/mouse) to mice. The mice were administered arctigenin (10, 40, or 150 mg/kg) or vehicle starting from the second day after amyloid ß1-42 injection to the end of the experiment. Behavioural tests were performed from days 9 to 15. On day 16 after the intracerebroventricular administration of amyloid ß1-42, the mice were sacrificed for biochemical analysis. Arctigenin (10-150 mg/kg) significantly attenuated the impairment of spontaneous alternation behaviours in the Y-maze task, decreased the escape latency in the Morris water maze test, and increased the swimming times and swimming distances to the platform located in the probe test. Arctigenin attenuated the level of phosphorylated tau at the Thr-181, Thr-231, and Ser-404 sites in the hippocampus, and increased the phosphorylation levels of phosphatidylinositol-3-kinase, threonine/serine protein kinase B, and glycogen synthase kinase-3ß. Arctigenin effectively provides protection against learning and memory deficits and in inhibits hyperphosphorylated tau protein expression in the hippocampus. The possible mechanism may occur via the phosphatidylinositol-3-kinase/protein kinase B-dependent glycogen synthase kinase-3ß signalling pathway.

Anti-inflammatory effects of Neurotoxin-Nna, a peptide separated from the venom of Naja naja atra.

BACKGROUND: Neurotoxin-Nna (NT), an analgesic peptide separated from the venom of Naja naja atra, has reported to have an exceptional specificity to block transmission of the nerve impulse by binding to the α- subunit of the nicotinic acetylcholine receptor in the membrane. However, little information is available on the anti-inflammatory effects of NT. Therefore, the anti-inflammatory activity of Neurotoxin-Nna was investigated in this study. METHODS: The anti-inflammatory effects of NT were evaluated by measuring its influence on several crucial factors in inflammatory pathways, including total antioxidant activity, antinociceptive effects in vivo, nuclear factor kappa B (NF-κB), polymorphonuclear cells (PMN), inducible nitric oxide synthase (iNOS), adhesion molecule (ICAM-1) and tactile hyperalgesia. RESULTS: NT treatment decreased the levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß). NT treatment decreased the total antioxidant status (TAOS) and reduced CFA-induced tactile hyperalgesia in a dose-dependent manner. NT significantly inhibited regulation of NF-kappaB activation and the production of IL-1ß, TNF-α, iNOS and CAM-1. Moreover, NT suppressed infiltration of PMN. CONCLUSIONS: Our results showed that NT reduced CFA-induced tactile hyperalgesia through inhibition inflammatory pathways in experimental inflammatory rats.